We are primarily engaged in four physico-chemical approaches to understanding why deoxy sickle hemoglobin (HbS) gels when sufficiently concentrated at temperatures above about 13 degrees, and normal hemoglobin (HbA) does not. Our main effort is in studying viscosity-changes, changes in light-scattering, in electrical birefringence relaxation, and in solubility, all of them as affected by various environmental parameters. Both rates and equilibria are beingstudied. Our present state of accomplishment makes available sophisticated instrumentation of proven worth, for the first three of these methods. Results with both viscosity and bire-fringence relaxation are at the publication stage. Our principal finding is the demonstration that gelling requires two successive processes: (a) an initial reaction which is highly sensitive to temperature, but which does not affect viscosity; and (b) a rapid process which is hardly affected by temperature, in which the viscosity rises very rapidly after completion of the initial phase which appears to represent highly concerted aggregation without change of shape or compactness. We have also shown that the formation of get is not the terminal stage of the second process: light-scattering shows that it continues after gels are formed. During the second year work will be started on an important parameter: the effect on the above processes of mixing other forms of normal human hemoglobin with deoxy S. The results should help distinguish between a number of alternative mechanisms for gelling suggested by our viscosity work.